Farhoodi Henry P, Segaliny Aude I, Wagoner Zachary W, Cheng Jason L, Liu Linan, Zhao Weian
Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA.
Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA 92697, USA.
J Bone Oncol. 2020 May 31;23:100298. doi: 10.1016/j.jbo.2020.100298. eCollection 2020 Aug.
Many cancers metastasize to the bones, particularly in cases of breast and prostate cancers. Due to the "vicious cycle" of cancer cells inducing bone resorption, which promotes further tumor growth, they are difficult to treat and may lead to extreme pain. These factors increase the urgency for emerging therapeutics that target bone metastases more specifically and effectively. Animal studies are essential to the development of any therapeutics, but also require robust animal models of human diseases. Robust animal models are often challenging to develop in the case of bone metastasis studies. Previous methods to induce bone metastasis include intracardiac, intravenous, subcutaneous via mammary fat pad, and intraosseous cancer cell injections, but these methods all have limitations. By contrast, the caudal artery route of injection offers more robust bone metastasis, while also resulting in a lower rate of vital organ metastases than that of other routes of tumor implantation. A syngeneic animal model of bone metastasis is necessary in many cancer studies, because it allows the use of immunocompetent animals, which more accurately mimic cancer development observed in immunocompetent humans. Here we present a detailed method to generate robust and easily monitored 4T1-CLL1 syngeneic bone metastases with over 95% occurrence in BALB/c mice, within two weeks. This method can potentially increase consistency between animals in bone cancer metastasis studies and reduce the number of animals needed for studying bone metastases in mice.
许多癌症会转移至骨骼，尤其是乳腺癌和前列腺癌病例。由于癌细胞诱导骨吸收的“恶性循环”会促进肿瘤进一步生长，这些癌症难以治疗，且可能导致剧痛。这些因素增加了对更具针对性且有效的骨转移靶向新兴疗法的迫切需求。动物研究对任何疗法的开发都至关重要，但也需要强大的人类疾病动物模型。在骨转移研究中，开发强大的动物模型往往具有挑战性。以往诱导骨转移的方法包括心内注射、静脉注射、经乳腺脂肪垫皮下注射和骨内癌细胞注射，但这些方法都有局限性。相比之下，尾动脉注射途径能产生更强的骨转移，同时与其他肿瘤植入途径相比，重要器官转移率更低。在许多癌症研究中，同基因骨转移动物模型是必要的，因为它允许使用具有免疫活性的动物，能更准确地模拟在具有免疫活性的人类中观察到的癌症发展情况。在此，我们展示一种详细方法，可在两周内生成强大且易于监测的4T1-CLL1同基因骨转移模型，在BALB/c小鼠中的发生率超过95%。该方法可能会提高骨癌转移研究中动物之间的一致性，并减少研究小鼠骨转移所需的动物数量。
